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A review of predictive, prognostic and diagnostic biomarkers for non-small-cell lung cancer: towards personalised and targeted cancer therapy

Published online by Cambridge University Press:  25 November 2019

Ernest Osei*
Affiliation:
Grand River Regional Cancer Centre, Department of Medical Physics, Kitchener, ON, Canada Department of Physics and Astronomy Department of Systems Design Engineering, University of Waterloo, Waterloo, ON, Canada Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON Canada
Julia Lumini
Affiliation:
Department of Biology, University of Waterloo, Waterloo, ON, Canada
Dinindu Gunasekara
Affiliation:
Department of Physics and Astronomy
Beverley Osei
Affiliation:
Department of Health Sciences, McMaster University, Hamilton, ON, Canada
Akua Asare
Affiliation:
Department of General Science, Brock University, St. Catherines, ON, Canada
Raymond Laflamme
Affiliation:
Institute for Quantum Computing, University of Waterloo, Waterloo, ON, Canada
*
Author for correspondence: Ernest Osei, Grand River Regional Cancer Centre, Department of Medical Physics, Kitchener, ON, Canada; Department of Physics and Astronomy, University of Waterloo, Department of Systems Design Engineering, University of Waterloo, Waterloo, ON, Canada; Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON Canada. E-mail: ernest.osei@grhosp.on.ca

Abstract

Introduction:

Lung cancer has a high mortality rate mainly due to the lack of early detection or outward signs and symptoms, thereby often progressing to advanced stages (e.g., stage IV) before it is diagnosed. However, if lung cancers can be diagnosed at an early stage and also if clinicians can prospectively identify patients likely to respond to specific treatments, then there is a very high potential to increase patients’ survival. In recent years, several investigations have been conducted to identify cancer biomarkers for lung cancer risk assessment, early detection and diagnosis, the likelihood of identifying the group of patients who will benefit from a particular treatment and monitoring patient response to treatment.

Materials and Methods:

This paper reports on the review of 19 current clinical and emerging biomarkers used in risk assessment, screening for early detection and diagnosis and monitoring the response of treatment of non-small-cell lung cancers.

Conclusion:

The future holds promise for personalised and targeted medicine from prevention, diagnosis to treatment, which take into account individual patient’s variability, though it depends on the development of effective biomarkers interrogating the key aberrant pathways and potentially targetable with molecular targeted or immunologic therapies. Lung cancer biomarkers have the potential to guide clinical decision-making since they can potentially detect the disease early, measure the risk of developing the disease and the risk of progression, provide accurate information of patient response to a specific treatment and are capable of informing clinicians about the likely outcome of a cancer diagnosis independent of the treatment received. Moreover, lung cancer biomarkers are increasingly linked to specific molecular pathway deregulations and/or cancer pathogenesis and can be used to justify the application of certain therapeutic or interventional strategies.

Type
Literature Review
Copyright
© Cambridge University Press 2019

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References

Canadian Cancer Society. What is lung cancer? 2019. https://www.cancer.ca/en/cancer-information/cancer-type/lung/lung-cancer/?region=on. Accessed on 17th April 2019.Google Scholar
Zamay, T, Zamay, G, Kolovskaya, O et al. Current and prospective protein biomarkers of lung cancer. Cancers 2017; 9 (11): 155.CrossRefGoogle ScholarPubMed
Polanski, J, Chabowski, M, Jankowska-Polanska, B, Janczak, D, Rosinczuk, J. Histological subtype of lung cancer affects acceptance of illness, severity of pain, and quality of life. J Pain Res 2018; 11: 727733. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903479/. doi: 10.2147/JPR.S155121.CrossRefGoogle Scholar
Li, X, Asmitananda, T, Gao, L et al. Biomarkers in the lung cancer diagnosis: a clinical perspective. Neoplasma 2012; 59(5): 500507.CrossRefGoogle ScholarPubMed
Ostrowski, M, Marjanski, T, Rzyman, W. Low-dose computed tomography screening reduced lung cancer mortality. Adv Med Sci 2018; 63(2): 230236. https://www.sciencedirect.com/science/article/pii/S1896112617300834?via%3Dihub. doi: 10.1016/j.advms.2017.12.002.CrossRefGoogle Scholar
Greenberg, A K, Lee, M S. Biomarkers for lung cancer: clinical uses. Curr Opin Pulm Med 2007; 13 (4): 249255.CrossRefGoogle ScholarPubMed
WHO, World Health Organization, International Programme on Chemical Safety. Biomarkers and risk assessment: concepts and principles, 1993.Google Scholar
Goossens, N, Nakagawa, S, Sun, X, Hoshida, Y. Cancer biomarker discovery and validation. Transl Cancer Res 2015; 4 (3): 256269. doi: 10.3978/j.issn.2218-676X.2015.06.04.Google Scholar
Duffy, M J, O’Donovan, N, Crown, J. Use of molecular markers for predicting therapy response in cancer patients. Cancer Treat Rev 2011; 37 (2): 151159.CrossRefGoogle ScholarPubMed
Ballman, K V. Biomarker: predictive or prognostic? J Clin Oncol 2015; 33 (33): 39683971.CrossRefGoogle ScholarPubMed
Villalobos, P, Wistuba, II. Lung cancer biomarkers. Hematol Oncol Clin 2017; 31 (1): 1329.CrossRefGoogle ScholarPubMed
Khalil, F K, Altiok, S. Advances in EGFR as a predictive marker in lung adenocarcinoma. Cancer Control 2015: 193199. doi: 10.1177/107327481502200210.CrossRefGoogle Scholar
Hodoglugil, U, Carrillo, M W, Hebert, J M, et al. PharmGKB summary: very important pharmacogene information for the epidermal growth factor receptor. Pharmacogenet Genomics 2013; 23 (11): 636642. doi: 10.1097/FPC.0b013e3283655091.CrossRefGoogle ScholarPubMed
da Cunha Santos, G, Shepherd, F A, Tsao, M S. EGFR mutations and lung cancer. Ann Rev Pathol Mech Dis 2011; 6: 4969.CrossRefGoogle ScholarPubMed
Yarden, Y. The EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities. Eur J Cancer 2001; 37: 38.CrossRefGoogle ScholarPubMed
Oda, K, Matsuoka, Y, Funahashi, A, Kitano, H. A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 2005; 1 (1): 2005.0010.CrossRefGoogle ScholarPubMed
Syrigos, K N, Georgoulias, V, Zarogoulidis, K, Makrantonakis, P, Charpidou, A, Christodoulou, C. Epidemiological characteristics, EGFR status and management patterns of advanced non-small cell lung cancer patients: the Greek REASON observational registry study. Anticancer Res 2018; 38 (6): 37353744.CrossRefGoogle ScholarPubMed
Ahmadzada, T, Kao, S, Reid, G, Boyer, M, Mahar, A, Cooper, W A. An update on predictive biomarkers for treatment selection in non-small cell lung cancer. J Clin Med 2018; 7 (6): 153. Published 2018 June 15. doi: 10.3390/jcm7060153.CrossRefGoogle ScholarPubMed
Martínez-Carretero, C, Pascual, F I, Rus, A, Bernardo, I. Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods. Clin Chem Lab Med (CCLM) 2017; 55 (12): 19701978.CrossRefGoogle ScholarPubMed
Mok, T S, Wu, Y L, Thongprasert, S et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361 (10): 947957.CrossRefGoogle ScholarPubMed
Zhang, Q, Nong, J, Wang, J et al. Isolation of circulating tumor cells and detection of EGFR mutations in patients with non-small-cell lung cancer. Oncol Lett 2019; 17 (4): 37993807.Google ScholarPubMed
Douillard, J Y, Ostoros, G, Cobo, M et al. Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free tumor DNA as a surrogate for determination of EGFR status. J Thorac Oncol. 2014; 9 (9): 13451353.CrossRefGoogle ScholarPubMed
Wu, Y L, Chu, D T, Han, B et al. Phase III, randomized, open-label, first-line study in Asia of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer: evaluation of patients recruited from mainland China. Asia Pac J Clin Oncol 2012; 8 (3): 232243. doi: 10.1111/j.1743-7563.2012.01518.x. Epub 2012 April 23.CrossRefGoogle ScholarPubMed
Fukuoka, M, Wu, Y L, Thongprasert, S et al. Biomarker analyses and final overall survival results from a phase iii, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non–small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011; 29 (21): 28662874. doi: 10.1200/JCO.2010.33.4235.CrossRefGoogle Scholar
Maemondo, M, Inoue, A, Kobayashi, K et al. Gefitinib or chemotherapy for non–small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362 (25): 23802388.CrossRefGoogle ScholarPubMed
Demuth, C, Madsen, A T, Weber, B, Wu, L, Meldgaard, P, Sorensen, B S. The T790M resistance mutation in EGFR is only found in cfDNA from erlotinib-treated NSCLC patients that harbored an activating EGFR mutation before treatment. BMC Cancer 2018; 18 (1): 191.CrossRefGoogle ScholarPubMed
Jean, S, Kiger, A A. Classes of phosphoinositide 3-kinases at a glance. J Cell Sci 2014; 127(Pt 5): 923928. doi: 10.1242/jcs.093773.CrossRefGoogle ScholarPubMed
Chaft, J E, Arcila, M E, Paik, P K et al. Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma–rationale for comprehensive mutation profiling. Mol Cancer Ther 2012; 11 (2): 485491.CrossRefGoogle ScholarPubMed
Scheffler, M, Bos, M, Gardizi, M et al. PIK3CA mutations in non-small cell lung cancer (NSCLC): genetic heterogeneity, prognostic impact and incidence of prior malignancies. Oncotarget 2015; 6 (2): 1315.CrossRefGoogle ScholarPubMed
Spoerke, J M, O’Brien, C, Huw, L et al. Phosphoinositide 3-Kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models. Clin Cancer Res 2012; 18 (24): 67716783. doi: 10.1158/1078-0432.CCR-12-2347.CrossRefGoogle ScholarPubMed
Massacesi, C, Di Tomaso, E, Urban, P et al. PI3K inhibitors as new cancer therapeutics: implications for clinical trial design. Onco Targets Therapy 2016; 9: 203.CrossRefGoogle ScholarPubMed
Vansteenkiste, J F, Canon, J L, De Braud, F et al. Safety and efficacy of buparlisib (BKM120) in patients with PI3K pathway-activated non-small cell lung cancer: results from the phase II BASALT-1 study. J Thorac Oncol 2015; 10 (9): 13191327.CrossRefGoogle ScholarPubMed
Chiarle, R, Voena, C, Ambrogio, C, Piva, R, Inghirami, G. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer 2008; 8 (1): 11.CrossRefGoogle ScholarPubMed
Kwak, E L, Bang, Y J, Camidge, D R et al. Anaplastic lymphoma kinase inhibition in non–small-cell lung cancer. N Engl J Med 2010; 363 (18): 16931703.CrossRefGoogle ScholarPubMed
Du, X, Shao, Y, Qin, H F, Tai, Y H, Gao, H J. ALK-rearrangement in non-small-cell lung cancer (NSCLC). Thorac Cancer 2018; 9 (4): 423430.CrossRefGoogle Scholar
Zhang, Z, Shiratsuchi, H, Palanisamy, N, Nagrath, S, Ramnath, N. Expanded CTCs from a patient with ALK positive lung cancer present EML4-ALK rearrangement along with resistance mutation and enable drug sensitivity testing: a case study. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 2017; 12 (2): 397.Google ScholarPubMed
McCoach, C E, Blakely, C M, Banks, K C et al. Clinical utility of cell-free DNA for the detection of ALK fusions and genomic mechanisms of ALK inhibitor resistance in non–small cell lung cancer. Clin Cancer Res 2018; 24 (12): 27582770.CrossRefGoogle ScholarPubMed
Arcila, M E, Drilon, A, Sylvester, B E et al. MAP2K1 (MEK1) mutations define a distinct subset of lung adenocarcinoma associated with smoking. Clin Cancer Res 2015; 21 (8): 19351943.CrossRefGoogle ScholarPubMed
Marks, JL, Gong, Y, Chitale, D et al. Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma. Cancer Res 2008; 68 (14): 55245528.CrossRefGoogle ScholarPubMed
Kim, C, Giaccone, G. MEK inhibitors under development for treatment of non-small-cell lung cancer. Expert Opin Invest Drugs 2018; 27 (1): 1730.CrossRefGoogle ScholarPubMed
Mas, C, Boda, B, Caulfuty, M et al. Antitumour efficacy of the selumetinib and trametinib MEK inhibitors in a combined human airway-tumour–stroma lung cancer model. J Biotechnol 2015; 205: 111119.CrossRefGoogle Scholar
Chen, Z, Cheng, K, Walton, Z et al. A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response. Nature 2012; 483: 613617.CrossRefGoogle ScholarPubMed
Huang, M, Lee, J, Chang, Y et al. MEK inhibitors reverse resistance in epidermal growth factor receptor mutation lung cancer cells with acquired resistance to gefitinib. Mol Oncol 2013; 7: 112120.CrossRefGoogle ScholarPubMed
Troiani, T, Vecchione, L, Martinelli, E et al. Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by CAMP-dependent protein kinase a activation in human lung and colorectal cancer cells. Br J Cancer 2012; 106: 16481659.CrossRefGoogle ScholarPubMed
Furlan, A, Kherrouche, Z, Montagne, R, Copin, M, Tulasne, D. Thirty years of research on MET receptor to move a biomarker from bench to bedside. Cancer Res. 2014. doi: 10.1158/0008-5472.CAN-14-1932.CrossRefGoogle Scholar
Schmitz, K, Koeppen, H, Binot, E et al. MET gene copy number alterations and expression of MET and hepatocyte growth factor are potential biomarkers in angiosarcomas and undifferentiated pleomorphic sarcomas. PLoS One 2015; 10 (4): e0120079. doi: 10.1371/journal.pone.0120079.CrossRefGoogle ScholarPubMed
Zhang, Y, Du, Z, Zhang, M. Biomarker development in MET targeted therapy. Oncotarget 2016; 7 (24): 3737037390.CrossRefGoogle ScholarPubMed
Zhang, J, Babic, A. Regulation of the MET oncogene: molecular mechanisms. Carcinogenesis 2016; 37 (4): 345355.CrossRefGoogle ScholarPubMed
Salgia, R. MET in lung cancer: biomarker selection based on scientific rationale. Mol Cancer Ther 2017; 16 (4): 555565. doi: 10.1158/1535-7163.MCT-16-0472.CrossRefGoogle ScholarPubMed
Smolen, G A, Sordella, R, Muir, B et al. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. PNAS 2006; 103 (7): 23162321. doi: 10.1073_pnas.0508776103.CrossRefGoogle ScholarPubMed
Matsumoto, K, Umitsu, M, De Silva, D M, Roy, A, Bottaro, D P. Hepatocyte growth factor/MET in cancer progression and biomarker discovery. Cancer Sci 2007; 108 (3): 296307. doi: 10.1111/cas.13156.CrossRefGoogle Scholar
Roudi, R, Kalantar, E, Keshtkar, A, Madjd, Z. Accuracy of c-KIT in lung cancer prognosis; a systematic review protocol. Asian Pac J Cancer Prev 2016; 17 (2): 863866. doi: 10.7314/APJCP.2016.17.2.863.CrossRefGoogle ScholarPubMed
Patel, J N, Ersek, J L, Kim, E S. Lung cancer biomarkers, targeted therapies and clinical assays. Transl Lung Cancer Res 2015; 4 (5): 503514. doi: 10.3978/j.issn.2218-6751.2015.06.02.Google ScholarPubMed
Xu, C, Wang, W, Zhang, Q et al. P3.03-09 molecular spectrum of KIT mutations detection in Chinese non-small cell lung cancer patients. J Thorac Oncol 2018; 13 (10): S913S914. doi: 10.1016/j.jtho.2018.08.1686.Google Scholar
Donnenberg, A D, Zimmerlin, L, Landreneau, R J, Luketich, J D, Donnenberg, V S. KIT (CD117) expression in a subset of non-small cell lung carcinoma (NSCLC) patients. PLoS One 2012; 7 (12): e52885. doi: 10.1371/journal.pone.0052885.CrossRefGoogle Scholar
Perumal, D, Pillai, S, Nguyen, J, Schaal, C, Coppola, D, Chellappan, S P. Nicotinic acetylcholine receptors induce c-Kit ligand/stem cell factor and promote stemness in an ARRB1/B-arrestin-1 dependent manner in NSCLC. Oncotarget 2014; 5 (21): 1048610502.CrossRefGoogle Scholar
Yoo, J, Kim, C H, Song, S H et al. Expression of c-kit and p53 in non-small cell lung cancers. Cancer Res Treat 2004; 36 (3): 167172. doi: 10.4143/crt.2004.36.3.167 CrossRefGoogle ScholarPubMed
Xu, C, Buczkowski, K A, Zhang, Y et al. NSCLC driven by DDR2 mutation is sensitive to dasatinb and JQ1 combination therapy. Mol Cancer Ther 2015; 14 (10): 23822389. doi: 10.1158/1535-7163.MCT-15-0077.CrossRefGoogle Scholar
Sasaki, H, Shitara, M, Yokota, K et al. DDR polymorphisms and mRNA expression in lung cancers of Japanese patients. Oncol Lett 2012; 68 (4): 3337. doi: 10.3892/ol/2012.684.CrossRefGoogle Scholar
Terai, H, Tan, L, Beauchamp, E M et al. Characterization of DDR2 inhibitors for the treatment of DDR2 mutated NSCLC. Am Chem Soc Chem Biol 2015; 10: 26872696. doi: 10.1021/acschembio.5b00655.Google Scholar
Lee, M S, Jung, E A, An, S B et al. Prevalence of mutation in DDR2 in squamous cell lung cancers in Korean patients. Korean Cancer Assoc 2017; 49 (4): 10651076. doi: 10.4143/crt2016.347.Google ScholarPubMed
Kobayashi-Watanabe, N, Sato, A, Watanabe, T et al. Functional analysis of discoidin domain receptor 2 mutation and expression in squamous cell lung cancer. Lung Cancer 2017; 101: 3541. doi: 10.1016/j.lungcan.2017.05.017.CrossRefGoogle Scholar
Beauchamp, E M, Woods, B A, Dulak, A M et al. Acquired resistance to dasatinib in lung cancer cell lines conferred by DDR2 gatekeeper mutation and NF1 loss. Mol Cancer Ther 2013; 13 (2): 475482. doi: 10.1158/1535-7163.MCT-13-0817.CrossRefGoogle ScholarPubMed
Kim, D, Ko, P, You, E, Rhee, S. The intracellular juxtamembrane domain of discoidin domain receptor 2 (DDR2) is essential for receptor activation and DDR2-mediated cancer progression. Int J Cancer 2014; 135: 25472557.CrossRefGoogle ScholarPubMed
Rao, G, Pierobon, M, Kim, I K et al. Inhibition of AKT1 signaling promotes invasion and metastasis of non-small cell lung cancer cells with K-RAS or EGFR mutations. Sci Rep 2017; 7: 70667078. doi: 10.1038/s41598-017-06128-9.CrossRefGoogle ScholarPubMed
Malanga, D, Scrima, M, De Marco, C et al. Activating E17K mutation in the gene encoding the protein kinase AKT In a subset of squamous cell carcinoma of the lung. Cell Cycle 2008; 7 (5): 665669. doi: 10.4161/cc.7.5.5485.CrossRefGoogle Scholar
Do, H, Solomon, B, Michell, P L, Fox, S B, Dobrovic, A. Detection of the transforming AKT1 mutation E17K in non-small cell lung cancer by high resolution melting. BioMed Cent Res Notes 2008; 1: 14. doi: 10.1186/1756-0500-1-14.CrossRefGoogle ScholarPubMed
My Cancer Genome. Genetically informed cancer medicine. Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies. https://www.mycancergenome.org/content/clinical_trials/NCT01306045/.Google Scholar
Liu, L Z, Zhou, X D, Qian, G, Shi, X, Fang, J, Jiang, B H. AKT1 amplification regulates cisplatin resistance in human lung cancer cells through the mammalian target of Rapamycin/p70S6K1 pathway. Am Assoc Cancer Res J 2007; 67 (13): 63256332.CrossRefGoogle ScholarPubMed
Hollander, M C, Maier, C R, Hobbs, E A, Ashmore, A R, Linnoila, R I, Dennis, P A. Akt1 deletion prevents lung tumorigenesis by mutant K-ras. Oncogene 2011; 30 (15): 18121821. doi: 10.1038/onc.2010.556.CrossRefGoogle ScholarPubMed
Kim, M J, Kang, H G, Lee, S Y et al. AKT1 polymorphisms and survival of early stage NSCLC. J Surg Oncol 2012; 105: 167174. doi: 10.1002/jso.22071.CrossRefGoogle Scholar
Zhang, X, Fan, J, Li, Y et al. Polymorphisms in epidermal growth factor receptor (EGFR) and AKT1 as possible predictors of clinical outcomes in advanced NSCLC patients treated with EGFR TKIs. Tumor Biol 2016; 37: 10611069. doi: 10.1007/s13277-015-3893-1.CrossRefGoogle Scholar
Lee, S Y, Choi, J E, Jeon, H S et al. A panel of genetic polymorphism for the prediction of prognosis in patients with early stage NSCLC after surgical resection. PLoS One 2015; 10 (10): e0140216. doi: 10.1371/journal.pone.0140216.CrossRefGoogle Scholar
Knowles, P P, Murray-Rust, J, Kjær, S et al. Structure and chemical inhibition of the RET tyrosine kinase domain. J Biol Chem 2006; 281 (44): 3357733587.CrossRefGoogle ScholarPubMed
Wang, Y, Xu, Y, Wang, X et al. RET fusion in advanced non-small-cell lung cancer and response to cabozantinib: a case report. Med (Baltimore) 2019; 98 (3): e14120. doi: 10.1097/MD.0000000000014120.CrossRefGoogle ScholarPubMed
Mendoza, L. Clinical development of RET inhibitors in RET-rearranged non-small cell lung cancer: update. Oncol Rev 2018; 12 (2): 352.Google ScholarPubMed
Gozgit, J M, Chen, T H, Song, Y et al. RET fusions observed in lung and colorectal cancers are sensitive to ponatinib. Oncotarget 2018; 9 (51): 2965429664. doi: 10.18632/oncotarget.25664.CrossRefGoogle ScholarPubMed
Ju, Y S, Lee, W C, Shin, J Y, Lee, S, Bleazard, T, Won, J K. A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res 2012; 22 (3): 436445.CrossRefGoogle ScholarPubMed
Pao, W, Girard, N. New driver mutations in non-small-cell lung cancer. Lancet Oncol 2011; 12 (2); 175180.CrossRefGoogle ScholarPubMed
Garnett, M J, Marais, R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 2004; 6 (4): 313319.CrossRefGoogle ScholarPubMed
Alvarez, J G B, Otterson, G A. Agents to treat BRAF-mutant lung cancer. Drugs Context 2019; 8: 212566.Google ScholarPubMed
Marchetti, A, Felicioni, L, Malatesta, S et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol 2011; 29 (26): 35743579.CrossRefGoogle ScholarPubMed
Paik, P K, Arcila, M E, Fara, M et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 2011; 29 (15): 2046.CrossRefGoogle ScholarPubMed
Planchard, D, Kim, T M, Mazieres, J et al. Dabrafenib in patients with BRAF V600E-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol 2016; 17 (5): 642650. doi: 10.1016/S1470-2045(16)00077-2z.CrossRefGoogle ScholarPubMed
Ahmad, I, Iwata, T, Leung HY Mechanisms of FGFR-mediated carcinogenesis. Biochim Biophys Acta (BBA)-Mol Cell Res 2012; 1823 (4): 850860.CrossRefGoogle ScholarPubMed
Desai, A, Adjei, A A. FGFR signaling as a target for lung cancer therapy. J Thorac Oncol 2016; 11 (1): 920.CrossRefGoogle ScholarPubMed
Porta, R, Borea, R, Coelho, A et al. FGFR a promising druggable target in cancer: molecular biology and new drugs. Crit Rev Oncol Hematol 2017; 113: 256267.CrossRefGoogle ScholarPubMed
Ornitz, D M, Itoh, N. Fibroblast growth factors. Genome Biol 2001; 2 (3): 3005.13005.12.CrossRefGoogle ScholarPubMed
Weiss, J, Sos, M L, Seidel, D et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2010; 2: 62ra93.CrossRefGoogle ScholarPubMed
Helsten, T, Elkin, S, Arthur, E, Tomson, B N, Carter, J, Kurzrock, R. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res 2012; 22 (1); 259267.CrossRefGoogle Scholar
Quintanal-Villalonga, A, Molina-Pinelo, S, Cirauqui, C et al. FGFR1 cooperates with EGFR in lung cancer oncogenesis, and their combined inhibition shows improved efficacy. J Thorac Oncol 2019; 14 (4): 641655.CrossRefGoogle ScholarPubMed
Acquaviva, J, Smith, D L, Sang, J et al. Targeting KRAS-mutant non–small cell lung cancer with the Hsp90 inhibitor ganetespib. Mol Cancer Ther 2012; 11 (12): 26332643.CrossRefGoogle ScholarPubMed
Barbie, D A, Tamayo, P, Boehm, J S et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 2009; 462 (7269): 108.CrossRefGoogle ScholarPubMed
Zhang, J, Park, D, Shin, D M, Deng, X. Targeting KRAS-mutant non-small cell lung cancer: challenges and opportunities. Acta Biochim Biophys Sin 2015; 48 (1): 1116.Google ScholarPubMed
Jancík, S, Drábek, J, Radzioch, D, Hajdúch, M. Clinical relevance of KRAS in human cancers. Biomed Res Int 2010; 2010: 150960. doi: 10.1155/2010/150960.Google ScholarPubMed
Ferrer, I, Zugazagoitia, J, Herbertz, S, John, W, Paz-Ares, L, Schmid-Bindert, G. KRAS-Mutant non-small cell lung cancer: from biology to therapy. Lung Cancer 2018; 124: 5364. doi: 10.1016/j.lungcan. 2018.07.013.CrossRefGoogle Scholar
Roberts, P J, Stinchcombe, T E, Der, C J, Socinski, M A. Personalized medicine in non–small-cell lung cancer: is KRAS a useful marker in selecting patients for epidermal growth factor receptor–targeted therapy? J Clin Oncol 2010; 28 (31): 47694777.CrossRefGoogle Scholar
Riely, G J, Marks, J, Pao, W. KRAS mutations in non–small cell lung cancer. Proc Am Thorac Soc 2009; 6 (2): 201205.CrossRefGoogle ScholarPubMed
Román, M, Baraibar, I, López, I, et al. KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target. Mol Cancer 2018; 17 (1): 33. doi: 10.1186/s12943-018-0789-x.CrossRefGoogle ScholarPubMed
Janes, M R, Zhang, J, Li, L S et al. Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor. Cell 2018; 172 (3): 578589.CrossRefGoogle ScholarPubMed
Dompe, N, Klijn, C, Watson, S A et al. A CRISPR screen identifies MAPK7 as a target for combination with MEK inhibition in KRAS mutant NSCLC. PLoS One 2018; 13 (6): e0199264. doi: 10.1371/journal.pone.0199264.CrossRefGoogle ScholarPubMed
Gkountakos, A, Sartori, G, Falcone, I et al. PTEN in lung cancer: dealing with the problem, building on new knowledge and turning the game around. Cancers (Basel) 2019; 11 (8). pii: E1141. doi: 10.3390/cancers11081141.CrossRefGoogle ScholarPubMed
Lu, X X, Cao, L Y, Chen, X, Xiao, J, Zou, Y, Chen, Q. PTEN inhibits cell proliferation, promotes cell apoptosis, and induces cell cycle arrest via downregulating the PI3K/AKT/hTERT pathway in lung adenocarcinoma A549 cells. Biomed Res Int 2016; 2016: 2476842. doi: 10.1155/2016/2476842.CrossRefGoogle ScholarPubMed
Xiao, J, Hu, C P, He, B X et al. PTEN expression is a prognostic marker for patients with non-small cell lung cancer: a systematic review and meta-analysis of the literature. Oncotarget 2016; 7, 5783257840.CrossRefGoogle ScholarPubMed
Cully, M, You, H, Levine, A J, Mak, T W. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 2006; 6 (3): 184.CrossRefGoogle ScholarPubMed
Lim, W T, Zhang, W H, Miller, C R et al. PTEN and phosphorylated AKT expression and prognosis in early and late-stage non-small cell lung cancer. Oncol Rep 2007; 17: 853857.Google ScholarPubMed
Endoh, H, Yatabe, Y, Kosaka, T, Kuwano, H, Mitsudomi, T. PTEN and PIK3CA expression is associated with prolonged survival after gefitinib treatment in EGFR-mutated lung cancer patients. J Thorac Oncol 2006; 1: 629634.Google ScholarPubMed
Kucuk, Z Y, Charbonnier, L M, McMasters, R L, Chatila, T, Bleesing, J J. CTLA-4 haploinsufficiency in a patient with an autoimmune lymphoproliferative disorder. J Allergy Clin Immunol 2017; 140 (3): 862864.e4. doi: 10.1016/j.jaci.2017.02.032.CrossRefGoogle Scholar
Salama, A K, Hodi, F S. Cytotoxic T-lymphocyte-associated antigen-4. Clin Cancer Res 2011; 17 (14): 46224628. doi: 10.1158/1078-0432.CCR-10-2232. Epub 2011 April 5CrossRefGoogle ScholarPubMed
Grosso, J F, Jure-Kunkel, M N. CTLA-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immun 2013; 13: 5.Google ScholarPubMed
Formenti, S C, Rudqvist, N P, Golden, E et al. Radiotherapy induces responses of lung cancer to CTLA-4 blockade. Nat Med 2018; 24 (12); 18451851. doi: 10.1038/s41591-018-0232-2.CrossRefGoogle Scholar
Paulsen, E E, Kilvaer, T K, Rakaee, M et al. CTLA-4 expression in the non-small cell lung cancer patient tumor microenvironment: diverging prognostic impact in primary tumors and lymph node metastases. Cancer Immunol Immunother CII 2017; 66 (11): 14491461. doi: 10.1007/s00262-017-2039-2.CrossRefGoogle ScholarPubMed
Zhang, H Dutta, P Liu, J et al. Tumour cell-intrinsic CTLA 4 regulates PD-L1 expression in non-small cell lung cancer. J Cell Mol Med 2019; 23 (1): 535542. doi: 10.1111/jcmm.13956.CrossRefGoogle ScholarPubMed
Yu, H, Boyle, T A, Zhou, C, Rimm, D L, Hirsch, F R. PD-L1 expression in lung cancer. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 2016; 11 (7): 964975. doi: 10.1016/j.jtho.2016.04.014.Google ScholarPubMed
Jia, L, Zhang, Q, Zhang, R. PD-1/PD-L1 pathway blockade works as an effective and practical therapy for cancer immunotherapy. Cancer Biol Med. 2018; 15 (2): 116.Google ScholarPubMed
Meyers, D E, Bryan, P M, Banerji, S, Morris, D G. Targeting the PD-1/PD-L1 axis for the treatment of non-small-cell lung cancer. Curr Oncol 2018; 25 (4): e324e334. doi: 10.3747/co.25.3976.CrossRefGoogle ScholarPubMed
Ernani, V, Ganti, A K. Immunotherapy in treatment naïve advanced non-small cell lung cancer. J Thorac Disease 2018; 10 (Suppl 3): S412.CrossRefGoogle ScholarPubMed
Brahmer, J, Reckamp, K L, Baas, P et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N Engl J Med 2015; 373 (2): 123135.CrossRefGoogle ScholarPubMed
Gettinger, S, Horn, L, Jackman, D et al. Five-year follow-up of nivolumab in previously treated advanced non-small-cell lung cancer: results from the CA209-003 Study. J Clin Oncol 2018; 36 (17): 16751684. doi: 10.1200/JCO.2017.77.0412. Epub 2018 March 23.CrossRefGoogle ScholarPubMed
Pabani, A, Butts, C. Current landscape of immunotherapy for the treatment of metastatic non-small-cell lung cancer. Curr Oncol 2018; 25: S94S102. doi: 10.3747/co.25.3750.CrossRefGoogle ScholarPubMed
Pillai, R N, Behera, M, Berry, L D et al. HER2 mutations in lung adenocarcinomas: a report from the lung cancer mutation consortium. Cancer 2017; 123 (21): 40994105. doi: 10.1002/cncr.30869.CrossRefGoogle ScholarPubMed
Iqbal, N, Iqbal, N. Human Epidermal Growth Factor Receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Mol Biol Int 2014: 852748. doi: 10.1155/2014/852748.CrossRefGoogle Scholar
Takenaka, M, Hanagiri, T, Shinohara, S et al. The prognostic significance of HER2 overexpression in non-small cell lung cancer. Anticancer Res 2011; 31 (12): 46314636. Retrieved from http://ar.iiarjournals.org/content/31/12/4631.full.Google ScholarPubMed
Chandrashekhar, L. P. Targeted treatments emerge for HER2 mutations in lung cancer. Targeted Oncol 20th September 2018. Retrieved from https://www.targetedonc.com/publications/targeted-therapy-news/2018/september-2018/targeted-treatments-emerge-for-her2-mutations-in-lung-cancer.Google Scholar
Sehgal, K, Patell, R, Rangachari, D, Costa, D B. Targeting ROS1 rearrangements in non-small cell lung cancer with crizotinib and other kinase inhibitors. Transl Cancer Res 2018; 7 (Suppl 7): S779. doi: 10.21037/tcr.2018.08.11.CrossRefGoogle ScholarPubMed
Lin, J J, Shaw, A T. Recent advances in targeting ROS1 in lung cancer. J Thorac Oncol 2017; 12(11): 16111625. doi: 10.1016/j.jtho.2017.08.002.CrossRefGoogle ScholarPubMed
Kerr, K. ROS1 in lung cancer: ESMO biomarker factsheet. In: Global Survey of Phosphotyrosine Signalling Identifies Oncogenic Kinases in Lung Cancer. Retrieved from https://oncologypro.esmo.org/Education-Library/Factsheets-on-Biomarkers/ROS1-in-Lung-Caner.Google Scholar
Joshi, A, Pande, N, Noronha, V et al. ROS1 mutation non-small cell lung cancer-access to optimal treatment and outcomes. Ecancermedicalscience 2019; 13: 900. doi: 10.3332/ecancer.2019.900.CrossRefGoogle ScholarPubMed
Shaw, A T, Ou, S I, Bang, Y, Camidge, D R, Solomon, B J, Salgia, R. Crizotinib in ROS1- rearranged non-small-cell lung cancer. N Engl J Med 2017; 371 (21): 19631971. doi: 10.1056/NEJMoa1406766.CrossRefGoogle Scholar
Wu, Y L, Yang, J C, Kim, D W, et al. Phase II study of crizotinib in East Asian patients with ROS1-positive advanced non-small-cell lung cancer. J Clin Oncol 2018; 36: 14051411. [PubMed: 29596029].CrossRefGoogle ScholarPubMed
Amatu, A, Sartore-Bianchi, A, Siena, S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open 2016; 1: e000023. doi: 10.1136/esmoopen-2015-000023.CrossRefGoogle ScholarPubMed
Terry, J, De Luca, A, Leung, S et al. Immunohistochemical expression of neurotrophic tyrosine kinase receptors 1 and 2 in lung carcinoma. Arch Pathol Lab Med 2010; 135 (4): 433439. Retrieved from https://www.archivesofpathology.org/doi/pdf/10.1043/2010-0038-OA.1.Google Scholar
Marchiò, C, Scaltriti, M, Ladanyi, M et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol 2019; 30 (9): 14171427. doi: 10.1093/annonc/mdz204.CrossRefGoogle ScholarPubMed
Farago, A F, Taylor, M S, Doebele, R C et al. Clinicopathologic features of non-small-cell lung cancer harboring an NTRK1 gene fusion. JCO Precis Oncol 2018. doi: 10.1200/PO.18.00037.CrossRefGoogle Scholar
Farago, A A, Le, L P, Zheng, Z et al. Durable clinical response to entrectinib in NTRK1- rearranged non-small cell lung cancer. J Thorac Oncol 2015; 10 (12): 16701674. doi: 10.1097/01.JTO.0000473485.38553.f0.CrossRefGoogle ScholarPubMed
Hirsch, F R, Suda, K, Wiens, J, Bunn, P A. Jr New and emerging targeted treatments in advanced non - small - cell lung cancer. Lancet 2016; 388 (10048): 10121024. doi: 10.1016/S0140-6736(16)31473-8.CrossRefGoogle ScholarPubMed
Cocco, E, Scaltriti, M, Drilon, A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15 (12): 731747. doi: 10.1038/s41571-018-0113-0.CrossRefGoogle ScholarPubMed
Baeuerle, P A, Gires, O. EpCAM (CD326) finding its role in cancer. Br J Cancer 2007; 96 (3): 417.CrossRefGoogle ScholarPubMed
Kim, Y, Kim, H S, Cui, Z Y et al. Clinicopathological implications of EpCAM expression in adenocarcinoma of the lung. Anticancer Res 2009; 29 (5): 18171822.Google ScholarPubMed
Thompson, J C, Fan, R, Black, T et al. Measurement and immunophenotyping of pleural fluid EpCAM-positive cells and clusters for the management of non-small cell lung cancer patients. Lung Cancer 2019; 127: 2533. doi: 10.1016/j.lungcan.2018.11.020. Epub 2018 November 19.CrossRefGoogle ScholarPubMed
Went, P, Vasei, M, Bubendorf, L et al. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer 2006; 94 (1): 128135. doi: 10.1038/sj.bjc.6602924.CrossRefGoogle ScholarPubMed